Health Care Costs for Patients with Heart Failure Escalate Nearly 3-Fold in Final Months of Life

BACKGROUND: Heart failure (HF) is a severe chronic disease with growing prevalence and health care burden as well as high mortality. End-of-life cost data for patients with HF may inform disease and medication therapy management. OBJECTIVES: To (a) characterize a real-world sample of patients with HF who died; (b) estimate health care costs for 6 months and semiannually for 24 months, before death; and (c) examine associations between patient characteristics and predeath health care costs. METHODS: This was a retrospective study of commercial and Medicare Advantage with Part D (MAPD) enrollees (aged ≥ 18 years), using data from a large national health plan. Included patients had evidence of HF during January 1, 2009-December 31, 2013, based on ≥ 1 inpatient hospitalization or ≥ 2 noninpatient encounters with diagnosis code for HF and evidence of mortality during July 1, 2009-December 31, 2013. Demographic data, comorbidities, guideline-directed HF-related outpatient pharmacotherapy (HFRx), and predeath health care costs (all-cause and HF-related) were described. A generalized linear model examined associations between all-cause health care costs (months 6 and 1 previous to death) and specific patient characteristics. RESULTS: Of 48,026 identified patients, mean age was 77.9 years; 52.8% were female; 93.0% were MAPD enrolled; 92.5% had Quan-Charlson comorbidity score ≥ 3; and about one quarter (26.0%) had no evidence of HFRx. Over the last 6 months of life, monthly all-cause total cost increased 3.2-fold for MAPD enrollees and 2.8-fold for commercial enrollees, although pharmacy cost decreased slightly (0.8-fold for both plan types). Cumulative 6-month all-cause medical cost was $37,186 for MAPD enrollees and $143,363 for commercial enrollees (68.8% and 73.2% due to hospitalization, respectively), and cumulative HF-related medical cost was $20,794 for MAPD enrollees and $78,440 for commercial enrollees (88.8% and 95.3% due to hospitalization, respectively). Over the last 24 months, semiannual all-cause total cost increased 3.2-fold for MAPD enrollees and 4.5-fold for commercial enrollees, although pharmacy cost increased only slightly (1.1-fold and 1.3-fold, respectively). Based on multivariable analysis, factors associated with higher risk of incurring a cost increase between month 6 and month 1 before death included older age (75-84 years: cost ratio [CR] = 1.33, P < 0.001; ≥85 years: CR = 1.43, P < 0.001), comorbid coronary heart disease (CR = 1.12, P = 0.003), and no evidence of HFRx (CR = 1.48, P < 0.001). CONCLUSIONS: Patients with HF experienced ≥ 2.8-fold increase in monthly all-cause total cost over the last 6 months of life, which was driven by hospitalization. Although MAPD enrollees incurred greater cost increases, cumulative costs were higher for commercial enrollees. After multivariable adjustment, older age, comorbid coronary heart disease, and no evidence of HFRx were among factors associated with higher risk of cost increase over the last 6 months of life. Study findings provide predeath cost information that should be useful in value assessments of innovative HF interventions and highlight impact of HFRx on predeath health care costs.

H eart failure (HF) is a common and severe chronic disease, affecting approximately 5.7 million people within the United States, 1 and the prevalence is expected to exceed 8 million by 2030. 2 While HF already imposes substantial costs, total annual expenditures are expected to rise to $70 billion by 2030. 2 Despite notable technological achievements and improved survival over recent decades, patients with HF still experience high mortality rates. HF is, in fact, associated with a higher 5-year mortality rate (~50%) than most cancers. [3][4][5] Furthermore, mortality rates are high regardless of New York Heart Association (NYHA) functional class. 6 The 30-day and 1-year mortality rates after HF-related hospitalizations are 10% and 22%, respectively. 7 Because of the high mortality associated with HF, health care at the end of life must strike a challenging balance between patients' preferred quality of life, prolonged survival, and appropriate resource use/cost burden.
• Heart failure is a costly condition, rising in prevalence and incurring increasing cost burden to the health care system. • Despite notable technological achievements and improved survival over recent decades, patients with heart failure still experience high mortality rates. • Previous claims-based studies have shown that hospitalizations among patients with heart failure increase toward the end of life, but data are scarce regarding timing and nature of such increases, their associated costs, and characteristics of affected patients.

What is already known about this subject
• Patients with heart failure experienced steadily increasing costs over the final 24 months of life, with the sharpest increase within the final 6 months. • The factors associated with higher risk of cost increase between month 6 and month 1 included older age, comorbid coronary heart disease, and no evidence of heart failure-related outpatient pharmacotherapy, which was observed for approximately one quarter of patients. • Specific cost data were provided for up to 2 years before death, which will support decision making regarding heart failure interventions, such as outpatient pharmacotherapies, which can potentially prevent hospitalization and provide a clinically balanced offset of health care costs.

What this study adds
Patients were excluded if specific data points (gender, geographic region, or health plan type) were missing, or if the age at index date was ≥ 65 years among commercial enrollees. Patients were also excluded if enrollment in the health plan (with medical and pharmacy coverage) was not continuous for ≥ 6 months before death or if the patient had any claims dated > 45 days following the date of death. Subsets of patients were further identified based on continuous enrollment in the health plan (with medical and pharmacy coverage) for ≥ 12, ≥ 18, and ≥ 24 months before death.

Patient Characteristics and Health Care Costs
Patient characteristics, captured as of the index date, included age, gender, race/ethnicity, health plan type (MAPD or commercial health plan), and geographic region based on U.S. census classification. 10 Clinical characteristics captured during the 6 months before death included Quan-Charlson comorbidity score (grouped as 0, 1-2, 3-4, ≥ 5) and presence of specific comorbid conditions (hypertension, coronary heart disease [including myocardial infarction], chronic pulmonary disease, renal disease, atrial fibrillation, diabetes, and cerebrovascular disease [including stroke]). 11 Guideline-directed HF-related outpatient pharmacotherapy (HFRx) was also captured, 12 with a minimum requirement of 14 days supplied. The regimens were noted by treatment pattern with specific medications among the following possible combinations: (a) beta blocker alone (i.e., no evidence of angiotensin-converting enzyme inhibitor [ACE-I]/angiotensin-receptor blocker [ARB] or aldosterone receptor antagonist (AA); (b) AA alone (i.e., no evidence of ACE-I/ARB or beta blocker); (c) ACE-I/ARB alone (i.e., no evidence of AA or beta blocker); (d) ACE-I/ARB and beta blocker (i.e., no evidence of AA); (e) ACE-I/ARB and beta blocker and AA; (f) other HFRx; or (g) no evidence of HFRx (see Appendix, available in online article). Predeath all-cause and HF-related (only medical claims containing ICD-9-CM diagnosis codes for HF) health care costs were determined for combined health plan-paid and patient-paid amounts. Costs were calculated as monthly and cumulative costs during the 6 months before death. Cumulative 6-month costs were also calculated for 4 mutually exclusive periods during the 24 months before death (months 24-19, months 18-13, months 12-7, and months 6-1), requiring continuous enrollment for ≥ 24, ≥ 18, ≥ 12, and ≥ 6 months before death, respectively. Additionally, cumulative 24-month costs were calculated, requiring continuous enrollment for ≥ 24 months before death. Costs were categorized as total (medical plus pharmacy); medical (inpatient, ambulatory, emergency services, and other medical); and pharmacy. Costs were adjusted to 2013 U.S. dollars using the annual medical care component of the Consumer Price Index. 13 Although previous studies of patients with HF have reported a dramatic increase in resource use and costs in the final months of life, 8,9 limited information exists regarding the trends in specific costs in the 6-month period preceding death for patients with HF. Moreover, health care stakeholders may not fully appreciate or factor these costs in economic models or consequent decision making on value of innovative treatments. Real-world data from Medicare Advantage and commercial health plans can be used to quantify end-of-life costs in patients with HF, specify when they occur, and identify key drivers of such cost increases, including associated patient-and treatment-level factors. This cost information would provide useful insights to stakeholders for decision making, especially regarding economic assessment of disease and medication therapy management.
The objectives of this study were to (a) characterize a realworld sample of patients with HF who died; (b) estimate all-cause and HF-related health care costs for 6 months and semiannually for 24 months, before death; and (c) examine associations between patient characteristics and predeath health care costs.

■■ Methods Study Design and Data Source
This retrospective study examined patient characteristics and health care costs of enrollees in Medicare Advantage with Part D (MAPD) and commercial health plans. Pharmacy, medical, and enrollment data were leveraged using the Optum Research Database (ORD). The ORD accesses administrative claims data for 500,000 Medicare Advantage enrollees and approximately 14 million commercial enrollees annually, resulting in a geographically diverse sample from across the United States. In addition, mortality data from the Social Security Administration (SSA) death master file (DMF; to supplement claims-based evidence of death) and race/ethnicity information were merged with the ORD. This study was conducted in compliance with the Health Insurance Portability and Accountability Act privacy rules.

Study Sample
Patients were included if they had evidence of HF during January 1, 2009-December 31, 2013, based on having either ≥ 1 inpatient hospitalization or ≥ 2 noninpatient encounters on 2 separate dates with diagnosis codes for HF (International

Data Analysis
Patient characteristics (demographic and clinical) were described separately for individuals with continuous enrollment in their health plans for ≥ 6 months and ≥ 24 months before death. Health care costs were stratified by health plan type. To account for the skewed distribution of the outcome (costs), generalized linear model (gamma distribution with log link) with repeated measures and a robust sandwich estimator (also known as robust covariance matrix estimator) to account for within-subject correlations was developed to examine associations between predeath health care costs (all-cause costs in months 6 and 1 before death) and specific patient and clinical characteristics. Independent variables were specified based on literature review 1,5,8 and availability in source data and included HFRx (during the 6 months before death), age, gender, race/ethnicity, geographic region, health plan type, year of death, and comorbid conditions. Main effects evaluated association with costs for month 6 before death, and interactions evaluated association with increase in costs between month 6 and month 1 before death. A significance level of α = 0.05 was used to define statistical significance.

Patient Characteristics
After all study criteria were applied, the final study sample was composed of 48,026 patients, who had data available for the 6 months before their dates of death ( Figure 1). The demographic characteristics of the final study sample are presented in Table 1. The mean (standard deviation [SD]) age of patients as of 6 months before death was 77.9 (9.7) years, and 52.8% of patients were female. Among patients with continuous health plan enrollment for ≥ 6 months before death, most (93.0%) were enrolled in an MAPD health plan. Patients were predominantly from the South or Midwest geographic regions (70.8%) and were predominantly white (75.4%). The subset with continuous enrollment for ≥ 24 months before death was similar in composition to the overall sample. Among the study sample followed for 6 months before death, most (92.5%) patients had a Quan-Charlson comorbidity score of 3 or greater, and common comorbid conditions were hypertension (88.6%), coronary heart disease (67.9%), and chronic pulmonary disease (63.9%; Table 1). Approximately one quarter (26.0%) of patients had no evidence of HFRx during the 6 months before death. Among the patients who had evidence of HFRx during the 6 months before death (n = 35,557), therapy with ACE-I/ARB and beta blocker (i.e., no evidence of AA, 27.2%) was the most frequently observed regimen, followed by monotherapy beta blocker (i.e., no evidence of ACE-I/ARB, 17.2%). The magnitude of cost increases between month 6 and month 1 before death varied by cost category, with the sharpest increases during the 3 months before death. All-cause total cost rose 2.8-fold ($26,956) between month 6 and month 1 before death, with 2.9-and 3.5-fold increases for medical ($27,132) and inpatient ($24,173) costs, respectively, although all-cause pharmacy cost stayed relatively level. HF-related medical cost increased by a factor of 3.7 for medical and hospitalization costs.
For All-cause medical cost rose between the months 24-19 period to the months 6-1 period, by 4.9-fold ($114,314), with an even more pronounced increase in HF-related medical cost of 10.6-fold ($71,031; Figure 3B). All-cause pharmacy costs were relatively constant through the 24 months before death.
■■ Discussion HF imposes a substantial burden on society in terms of health care costs and high mortality rates. Although health care costs are generally known to rise toward the end of life, there is a knowledge gap regarding patterns of cost increases among The comorbidity and HFRx findings were similar for patients patients with continuous 24-month enrollment before death (n = 34,699). Briefly, the mean age was 78.2 (9.6) years; 53.9% of patients were female, and health plan and race/ethnicity distributions were the same as those having 6 months of enrollment. As for clinical characteristics, 92.7% of patients had a Quan-Charlson score of 3 or greater. Comorbidity proportions were the same, but just slightly fewer (23.1% compared with 26.0% among patients with 6-month enrollment) had no evidence of HFRx.

Predeath Health Care Costs
Medicare Advantage Enrollees. The magnitude of cost increases between month 6 and month 1 before death varied by cost category, with the highest increases for inpatient cost (Figure 2A). All-cause total cost rose 3.2-fold (increase of $8,451) between month 6 to month 1 before death, with inpatient cost rising 5.0-fold ($7,728) and medical cost rising 3.5-fold ($8,509) over the same interval. However, all-cause pharmacy cost remained relatively stable. HF-related medical cost increased 4.8-fold ($5,917) from month 6 to month 1 before death, with a 5.3-fold increase ($5,690) found for inpatient cost.
All-cause medical health care cost rose between the months 24-19 period to the months 6-1 period by 3.6-fold ($26,935), with an even more pronounced increase in HF-related medical cost of 6.2-fold ($17,464; Figure 2B). All-cause pharmacy costs were relatively constant through the 24 months before death.
Commercial Enrollees. For patients enrolled in a commercial health plan, expenditures also increased every month over the last 6 months of life ( Figure 3A). The mean (SD) cumulative all-cause medical cost for the 6-month period before death was $143,363 ($209,547), with nearly three quarters (73.2%) because of hospitalization ($104,877 [$192,481] 14 increased utilization, and costs nearing the end of life, 8,9 or the increased costs imposed by comorbid conditions associated with HF. 15,16 The characteristics of the current sample were similar to previous studies assessing costs associated with end-of-life care in HF. 8,9,15,16 The overall sample of patients for this study also had similarly high proportions with comorbid conditions, including hypertension, coronary heart disease, and chronic pulmonary disease. HF often presents with systemic complications that may  affect other comorbid conditions. Considering that comorbid conditions can also complicate the progression of HF, interactions between HF and comorbidities may increase health care costs, especially related to hospitalizations. 17,18 Also, approximately one fourth of patients in this study had no evidence of outpatient guideline-directed HFRx during the 6 months before death. This finding was notable given the emphasis placed on HFRx by the guidelines of American College of Cardiology Foundation/American Heart Association (ACC/AHA) Task Force on Practice Guidelines. 12 In this study, mean all-cause medical and inpatient costs over the 6 months before death were $37,186 and $25,600, respectively, for MAPD enrollees. These findings are comparable to medical ($36,216) and hospitalization costs ($20,309) reported by Unroe et al. (2011Unroe et al. ( ) using 2007 Medicare data. 9 The current study also revealed that costs attributed to inpatient hospitalizations comprised the greatest proportion of costs over the final 6 months before death. This finding is consistent with a recent community-based study that reported a dramatic increase in inpatient hospitalization resource use during the final 2 months, although that study did not report costs specifically. 8 Commercial enrollees had much higher expenditures than MAPD enrollees throughout the study period, most likely because of differences in cost structures between health plan types. Additionally, there was a greater increase in all-cause total cost for the MAPD patients than commercial enrollees over the final 6 months of life (3.2-fold and 2.8-fold, respectively), with particularly sharp increases in all-cause and HF-related inpatient costs.

All-Cause and Heart Failure-Related Costs for 6 Months Before Death and for Semiannual Periods up to 24 Months Before Death Among Commercial Enrollees
Another interesting finding is that over the final 6 months, just over one quarter of all-cause inpatient costs for MAPD and commercial enrollees (27.8% and 28.7%, respectively) were not attributable to HF-related inpatient costs, suggesting a substantial portion of these hospitalizations may be related to comorbid conditions. Previous studies have reported a link between comorbidity in patients with HF and higher hospitalization risk. Dunlay et al. (2015) reported that certain comorbidities were predictors of increased all-cause hospitalizations, including diabetes, chronic obstructive pulmonary disease, and peripheral vascular disease. 8 Unroe et al. found that comorbid conditions such as diabetes, chronic obstructive pulmonary disease, hypertension, and renal disease predicted increased costs, although the ratio of costs from month 6 to month 1 was not examined in their study. 9 Although the current study demonstrated HF-related care accounts for a large portion of all-cause costs, comorbid conditions may also be an important component, especially in the case of hypertension, which represents not only the most prevalent comorbid condition, but also the "most important modifiable risk factor for HF in the United States," according to the ACC/AHA Task Force on Practice Guidelines. 12 Semiannual all-cause total cost increased over the 24 months before death, with the sharpest increase between months 12-7 and months 6-1 (2.27-fold). No previous studies have reported costs for patients with HF up to 2 years before death. Study findings from examination of a longer time frame suggest a potential timeline for escalation of costs at end of life. This should be useful in evaluation of HF interventions that delay disease progression and mortality.
In multivariable analyses, the presence of either hypertension, diabetes, chronic pulmonary disease, or renal disease was associated with lower risk of cost increase between month 6 and month 1 before death. Further, these comorbid conditions were associated with increased cost risk for month 6 before death, and patients with these conditions were still at risk of cost increase between month 6 and month 1 before death. These results suggest value in further examining predeath health care use based on comorbidity profile/complexity for possible effect on health care costs. Aligned with findings from the descriptive analysis, the multivariable analyses suggested that no evidence of HFRx was associated with higher risk of cost increase between month 6 and month 1 before death (CR = 1.48, P < 0.001), as compared with receiving monotherapy ACE-I/ARB. Considering then that all-cause pharmacy costs remained relatively low and stable over the 6 months before death, accounting for less than 10% of cumulative all-cause total costs for MAPD and commercial enrollees, results suggest that optimized HFRx, as part of early interventions in disease management, may reduce health care costs for HF.

Limitations
Although this study provides important cost data regarding expenditures for patients with HF within 6 and 24 months before death, certain limitations may affect the interpretation of results. First, individuals in the studied sample were identified using data from health care administrative claims and the SSA DMF, neither of which are designed for research purposes; as such, identification may be imperfect because of coding/data input variation, and the presence of a diagnosis code on a claim does not represent proof of diagnosis. However, by including patients with ≥ 1 inpatient hospitalization or ≥ 2 non-inpatient encounters with diagnosis codes for HF, the likelihood that a patient was included who did not have HF was minimized.
Second, using the SSA DMF to confirm dates of death and limiting claims to those dated < 45 days after the date of death reduces the risk of erroneously including surviving patients in the sample. The DMF has known limitations because of degradation of the file starting in late 2011. We used the DMF file for confirmation of death; patients without evidence of death were not included in the final sample. The DMF file was not used to create absolute death rates or comparative rates of death in the sample.
Third, although guideline-directed HFRx was examined, patients may have received inotropic therapy, implantable cardioverter defibrillators, left ventricular assist devices, and cardiac resynchronization therapy, which were not examined in this study. Future studies should examine the contribution of such treatments to health care costs. Furthermore, claims data do not reflect over-the-counter medications, physicianprovided samples, or cash-purchased medications (i.e., without a pharmacy claim); thus, usage of HF-related pharmacotherapies may be underestimated. Also, information on ejection fraction, NYHA functional class, smoking, and body mass index were not available, which limited characterization of the overall health of the sample.
Fourth, covariates for the multivariate analyses were not collected in a baseline period, which hindered interpretation of causality. Finally, data were obtained from MAPD and commercially insured patients; therefore, findings may not be generalizable to patients with other insurance types or the uninsured.

■■ Conclusions
During the final 2 years of life, the highest cost burden occurred during the last 6 months before death for patients with HF. Across MAPD and commercial health plans, monthly all-cause total cost in patients with HF increased ≥ 2.8-fold over the last 6 months of life, with hospitalization being the main cost driver, and ≥ 3.2-fold over the last 24 months of life. After multivariable adjustment, older age, comorbid coronary heart disease, and having no evidence of HFRx were among factors associated with a higher risk of a cost increase over the last 6 months of life. Study findings provide predeath cost information that should be useful in value assessments of innovative HF interventions. They will also provide additional perspective to stakeholder discussions on the complexity and burden of end-of-life care among patients with HF and may reveal opportunities to reassess the role of HF pharmacotherapy in the context of end-of-life disease management.